Urinary tract infections (UTIs) are microbial infections which pose a significant public health threat. In 2007, there were 10.5 million outpatient UTI visits for medical care in the United States, and 21.3% of those visits were to emergency. UTIs are also prevalent worldwide, especially in countries with large populations and public sanitation challenges.
The United States Center for Disease Control and Prevention describes UTIs as infections that occur when a microbe enters the urinary tract. UTIs can arise from poor hygiene, intercourse, abnormal anatomy, and the presence of bacteria, virus or fungus. Some populations are at a higher risk of getting UTIs—women and girls have higher rates of UTIs than men due to anatomical structure. The elderly and patients with urinary incontinence or catheter implants are also at higher risk for UTIs. UTI symptoms are painful and have been described by patients as causing feelings of pain or burning while urinating, frequent urination and the feeling of a need to urinate despite having an empty bladder. Other common symptoms include low fever (about 38° C.), cloudy or bloody urine and pressure or cramping in the groin or lower abdomen. Further complicating accurate and timely diagnosis, UTI symptoms often present differently based on patient age. Infants with UTIs often present with a fever, fussy disposition, or reduced appetite. In contrast, elderly UTI patients may be asymptomatic or may exhibit symptoms resembling dementia, accompanied by excessive fatigue and incontinence. Despite the range of presentation, accurate and timely diagnosis is critical, as untreated UTIs can develop into more severe conditions such as kidney infections or sepsis.
In current practice, the diagnosis of UTIs involves clinical and physical exams, followed by both a sterile urinalysis and a positive urine culture test that usually takes multiple days to complete and often is not used in outpatient settings. Foxman B., “Epidemiology of urinary tract infections: incidence, morbidity, and economic costs”, American Journal of Medicine 113(1):5-13 (2002). This ‘gold standard’ procedure is followed for patients from whom a mid-stream urine sample can be collected. For patients who cannot urinate on their own, urine may be collected via a catheter, which is at the least uncomfortable and can be painful.
The urinalysis can be done relatively quickly and can tell providers whether an infection may be present in the urinary tract due to reading elevated levels of white blood cells in the sample, but it cannot identify the microbe causing the infection, quantify the level of infection or indicate the appropriate antibiotic.
The urine culture test detects the specific pathogens present, quantifies the microbial load, and can identify potential antibiotic resistance, but it takes substantial time. In this test, a urine sample is swabbed onto growth medium in a Petri plate. After a suitable incubation period to enable microbial replication, the Petri plate is visually inspected for microbes, which are then identified and quantified by a trained specialist. If looking for antibiotic resistance, multiple test plates may be made, with each subjected to a different antibiotic to test for resistance to that antibiotic. This approach has the advantage that it can find any type of microbe and look for any type of antibiotic resistance, but the disadvantage that the microbes must reproduce long enough to produce colonies visibly differentiable by the human eye. It takes a minimum of 18 hours, and often up to 72 hours, to obtain results from a urine culture test. Notably, when a urine culture test is run to diagnose a suspected UTI, as much as 80% of the time the test results are negative—that is, the test indicates that the patient does not have a UTI.
The lengthy time required for current urine culture tests results in very unsatisfactory treatment approaches. In most circumstances, and especially in pediatric or geriatric cases, clinicians tend to default-prescribe broad-spectrum antibiotics that cover a range of the microbes most commonly associated with UTIs, long before the urine culture test results are available. Since as much as 80% of the urine culture test results show no infection, this means that 80% of the patients are being prescribed antibiotics when they are of no value whatsoever. If subsequent urine culture test results indicate that the patient has a microbial infection, but not one susceptible to the antibiotic used initially, the original antibiotic will be discontinued and the correct antibiotic prescribed. This assumes the clinician can actually reach the patient at that point, which often is not the case.
In both the situation when the patient had no UTI, and the one when the patient has an infection that is not susceptible to the initial antibiotic, the patient is prescribed an ineffective antibiotic. This is not helpful for the patient and promotes the growth of antibiotic-resistant microbes.
In summary, UTIs are extremely common, but the current diagnosis and treatment processes are widely perceived as flawed by practitioners. In particular, the slow detection and quantification of the microbial load in a given infection by a urine culture test means that antibiotics are often prescribed to patients who do not actually have a UTI, and even in patients who do have a UTI, the initially prescribed antibiotics may target the wrong microbe or the microbe may be resistant to that antibiotic, requiring a post-test change in antibiotics. This extremely common issue contributes to antibiotic resistance, which increasingly threatens public health.
To improve treatment, a novel method of microbe detection, quantification and identification of antibiotic resistance is needed that works in hours instead of days, and that finds the correct treatment for at least the microbes known to frequently cause such infections, all at a reasonably low cost due to the high volume of tests required.